Recognition of Dextran鈥揝uperparamagnetic Iron Oxide Nanoparticle Conjugates (Feridex) via Macrophage Scavenger Receptor Charged Domains

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• 作者：Ying Chao ; Milan Makale ; Priya Prakash Karmali ; Yuriy Sharikov ; Igor Tsigelny ; Sergei Merkulov ; Santosh Kesari ; Wolf Wrasidlo ; Erkki Ruoslahti ; Dmitri Simberg
• 刊名：Bioconjugate Chemistry
• 出版年：2012
• 出版时间：May 16, 2012
• 年：2012
• 卷：23
• 期：5
• 页码：1003-1009
• 全文大小：363K
• 年卷期：v.23,no.5(May 16, 2012)
• ISSN：1520-4812

文摘

Dextran-coated superparamagnetic iron oxide nanoparticles (dextran鈥揝PIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic cells (HEK293T) to express major macrophage scavenger receptor (SR) subtypes including SR-AI, MARCO, and endothelial receptor collectin-12. These SRs possess a positively charged collagen-like (CL) domain and they promoted SPIO uptake, while the charge neutral lipoprotein receptor SR-BI did not. In silico modeling indicated a positive net charge on the CL domain and a net negative charge on the cysteine-rich (CR) domain of MARCO and SR-AI. In vitro experiments revealed that CR domain deletion in SR-AI boosted uptake of SPIO 3-fold, while deletion of MARCO鈥檚 CR domain abolished this uptake. These data suggest that future studies might productively focus on the validation and further exploration of SR charge fields in SPIO recognition.